1. Field of the Invention
The present invention relates to a process of preparing a biodegradable polymer using an enzyme catalyst and a biodegradable polymer prepared through the process.
2. Description of the Prior Art
A biodegradable polymer exemplified by poly(ε-caprolactone), poly(glycolic acid), poly(lactic acid), polyorthoester, polyphosphagene, and polypeptide is an polymer capable of being decomposed in vivo by a simple hydrolysis or enzyme action.
The melting point of poly(ε-caprolactone) is a low 59-64° C. and it has excellent solubility, and thus, it is mixed with other substances to be used as a biological substance. Furthermore, since it has a very slower biodegradation speed than poly(glycolic acid) or poly(lactic acid), it may be usefully applied to drug delivery system fields.
Since most biodegradable polymers are expensive, they are most often used as a high value-added medical material applied to an absorbent suture for stitching a wound, a tissue bonding agent, a bone grafting material, a drug delivery body, a tissue engineering or the like.
In a laboratory of Kobayashi Shiro, a professor of Kyoto University taking the initiative in studying the above field, with the development of a crystalline polymer “polyphenyleneoxide (PPO)” having superior heat resistance to polyphenylenesulfide (PPS) and generating only water as a byproduct at a low temperature of 40° C. and atmospheric pressure, commercialization of a “phenol resin containing an acetylene group” developed in partnership with Northeast Alps Co. has almost been completed. Furthermore, the laboratory is studying a process of preparing an polymer having superior properties to conventional polymer under moderate reaction conditions.
A process of preparing a biodegradable polymer is well known in the art, and Yadong Wang et al. suggest a process of preparing poly(glycerol-sebacate) (PGS) belonging to a biodegradable polymer which includes polycondensing glycerol and sebacic acid in the presence of a metal catalyst (Yadong Wang, Guillermo A. Ameer, Barbara J. Sheppard, Robert Langer, Nature Biotechnology, vol. 20, June 2002, 602-606). However, this process is problematic in that it is difficult to apply the process to humans because of use of a metal catalyst, and a complicated process, for example heating under reduced pressure, must be carried out.
In the course of studying development of a simple process which is not toxic to humans, many efforts have been focused on the production of a biodegradable polymer using an enzyme as a catalyst. Because the production of polymers using enzymes as catalysts is considered to help control specific polymer structure and expand functionality, many studies have been conducted worldwide. In detail, much effort has been made to develop a heat-resistant polymer, modify a conventional process of preparing a plastic, and provide novel functions in application fields.
An enzyme catalytic reaction is characterized in that the reaction is conducted at low temperatures and atmospheric pressure, a small amount of byproducts is generated, and only water and carbon dioxide are generated according to circumstances unlike a conventional polymerization reaction. The method of preparing a polymer having high performance and an polymer intermediate through an environmentally friendly enzyme-oxygen process is available, and an expectation of early commercialization of the method is growing.
Additionally, a promising organic reaction using an enzyme in vitro has aroused interest. The organic reaction using the enzyme is known to have the following three characteristics: one is that the reaction is carried out under moderate temperature, pressure, and pH conditions and energy efficiency is considered high, another is that it is possible to develop a novel reaction using regular stereochemistry in the pharmaceutical or agricultural chemistry fields, and the third is that a natural catalyst harmless to humans is employed, as is required in a green chemistry field.
The conventional process of preparing an polymer using an enzyme is classified into ring-open polymerization using lactones, polycondensation using diacid derivatives and diol, and polycondensation using hydroxyacid and ester. A lipase-catalysed acylation and elimination reaction is known as a case of an enzyme being used as a catalyst in a chemical reaction, and the enzyme is of high utility as a catalyst that is harmless to humans in the course of preparing substances applied to humans. However, in the case of polycondensation using diacid derivatives and diol, only diol having a primary alcohol group was used, but secondary alcohol has been scarcely studied.
Accordingly, the present inventors conducted a polycondensation of a polyhydric alcohol monomer having a secondary hydroxyl functional group and an acid monomer having a dicarboxylic group in the presence of an enzyme catalyst to prepare a biodegradable polymer, resulting in the finding that the biodegradable polymer is friendly to nature and it is possible to control the molecular weight by varying the reaction time in the course of the polymerization, thereby accomplishing the present invention.